William W. Thompson, PhD Immunization Safety Office Office of the Chief Science Officer Centers for Disease Control and Prevention Impact of Seasonal Influenza in the US

Collaborators David Shay, CDC Influenza Branch Eric Weintraub, CDC, OCSO/ISO Lynnette Brammer, CDC Influenza Branch Nancy Cox, CDC Influenza Branch Joe Bresee, CDC Influenza Branch Keiji Fukuda, WHO

Impact of Seasonal Influenza in the US Describe variation in deaths in US –Seasonal Variation –Age Variation Describe alternative models for estimating influenza-associated morbidity and mortality Compare alternative model estimates Review estimates of influenza impact –Deaths –Hospitalizations –Other morbidity

Seasonal Variation in Deaths Currently, there are approximately 2.4 million deaths in the United States annually –65,000 Underlying Pneumonia and Influenza deaths No direct measure of impact of influenza Strong seasonal component in US deaths –Peaks typically occur in December and January –Peaks tend to be associated with increases in influenza activity

Seasonal Variation in All-Cause Deaths ( ) Jun-71Jun-72 Jun-73 Jun-74 Jun-75Jun-76Jun-77Jun-78Jun-79Jun-80Jun-81Jun-82Jun-83Jun-84Jun-85Jun-86Jun-87 Jun-88Jun-89Jun-90Jun-91Jun-92 Jun-93 Jun-94 Jun-95Jun-96Jun-97Jun-98Jun-99Jun-00Jun-01Jun-02 Year Weekly All-Cause Deaths

Seasonal Variation in Underlying P&I Deaths ( ) Jun-71Jun-72Jun-73Jun-74Jun-75Jun-76Jun-77Jun-78Jun-79Jun-80Jun-81Jun-82Jun-83Jun-84Jun-85Jun-86Jun-87Jun-88Jun-89Jun-90Jun-91Jun-92Jun-93Jun-94Jun-95Jun-96Jun-97Jun-98Jun-99Jun-00Jun-01Jun-02 Year Weekly P&I Deaths

Population Growth in Urban Areas of the US Year Millions

Population Growth in Numbers of Elderly in the US Millions Age Group

Age Variation in Numbers of Deaths in the US , , , , , , , , Yrs 5-14 Yrs Yrs25-34 Yrs35-44 Yrs45-54 Yrs55-64 Yrs65-74 Yrs75-84 Yrs 85+ Yrs Age Group Deaths

RR of All-Cause Death Versus Underlying P&I Death (NCHS 2000) years 5-14 years years25-34 years35-44 years45-54 years55-64 years65-74 years75-84 years 85+ years Age Group RR of Death due to All-Cause versus P&I

Alternative Models for Estimating Impact of Influenza in US Simonsen et al. (1997) –Linear Regression Model –Modeled National Center for Health Statistics (NCHS) weekly death data from Outcomes –Underlying P&I Deaths (Most specific) –All-Cause Deaths (Least specific, most sensitive) Model Y t = a + b*t +c*t 2 + d*cos (2 t  /52) + f*sin(2 t  /52) + e t

Simonsen et al Model Jul-89Jul-90Jul-91Jul-92Jul-93Jul-94Jul-95 P&I Deaths

Alternative Models for Estimating Impact of Influenza in US Thompson et al. (2003) –Poisson Regression Model –Modeled National Center for Health Statistics (NCHS) weekly death data from –Incorporated WHO Influenza Surveillance Data Outcomes –Underlying P&I Deaths (Most specific) –Underlying Respiratory & Circulatory Deaths –All-Cause Deaths (Least specific) Model Y t =  exp (a + b*t +c*t 2 + d*cos (2 t  /52) + f*sin(2 t  /52) + g * A(H1N1)% + h * A(H3N2)% + i * B%)

Circulation of A(H3N2) Viruses and Underlying P&I Deaths Year P&I Deaths Per 100,000 A(H3N2)% Positive P&I Death RateA(H3N2)% % 10% 20% 30% 40% 50% 60%

Alternative Models for Estimating Impact of Influenza in US Barker & Mullooly (1980;1982) Two Types of Baseline Rates –Peri-Season Baseline Rate October through May when influenza is not circulating above 10% –Summer Season Baseline June through September Excess Rate = (Flu Rate) – (Non Flu Baseline Rate)

Seasonal Variation in Underlying P&I Deaths Summer Baseline Summer Baseline Winter Baseline Influenza Period Influenza Period Jul-89 Sep-89Nov-89 Jan-90 Mar-90 May-90 Jul-90 Sep-90Nov-90 Jan-91 Mar-91 May-91 Jul-91 Sep-91Nov-91 Jan-92 Mar-92 May-92 Jul-92

Influenza-Associated All-Cause Deaths by Model in the US ( ) Alternative Models Annual Influenza-Associated Deaths in US 31,467 29,473 43,958 73,635 35, ,000 20,000 30,000 40,000 50,000 60,000 70,000 80,000 Simonsen 97Simonsen 05PeriSummerPoisson

Correlations Between Estimates of Influenza- Associated All-Cause Deaths In the US ( ) Simonsen 97Simonsen 05PeriSummerPoisson Simonsen Simonsen Peri Summer Poisson

Correlation Between Estimates for Simonsen 2005 and Peri-Season Models y = x R 2 = Simonsen 2005 Estimates Peri Season Estimates

Influenza-Associated Underlying R&C Death Rates by Age For Peri-Season Model < >= 85 Age Group Deaths Per 100,000

Influenza-Associated Underlying R&C Deaths by Age For Peri-Season Model Age Group Influenza-Associated Deaths ,945 2,457 3,651 5,017 6,220 13, ,500 5,000 7,500 10,000 12,500 15,000 < >= 85

Surveillance of Influenza-Associated Deaths Among Children in the US 2003/2004 influenza season was severe compared to other recent seasons, especially among children CDC implemented surveillance of childhood deaths associated with influenza Reviewed case reports, medical records, autopsy reports

Surveillance of Influenza-Associated Deaths Among Children in the US Results –153 deaths among children aged < 18 years –96 deaths among children aged < 5 years –29% of the children died within 3 days of onset of the illness –47% of the children had previously been healthy CDC made influenza deaths among children a national reportable condition in October 2004

Influenza-Associated Hospitalizations Thompson et al (2004) National Hospital Discharge Survey Examined data from Incorporated WHO Influenza Surveillance data Outcomes –Primary P&I (Most Specific) –Any Listed P&I –Primary R&C –Any-Listed R&C (Least Specific) Model Y t =  exp (a + b*t +c*t 2 + d*cos (2 t  /12) + f*sin(2 t  /12) + g * A(H1N1)% + h * A(H3N2)% + i * B%)

Influenza-Associated Primary R&C Hospitalization Rates By Age ( ) < 5 Yrs 5-49 Yrs Yrs65-69 Yrs70-74 Yrs75-79 Yrs80-84 Yrs 85+ Yrs Age Group Influenza-Associated Primary R&C Hospitalizations Per 100,000

Influenza-Associated Primary R&C Hospitalizations By Age ( ) Age Group Influenza-Associated Primary R&C Hospitalizations 20,031 34,867 29,447 18,301 26,501 27,516 28,578 40, ,000 20,000 30,000 40,000 50,000 < 5 Yrs 5-49 Yrs Yrs65-69 Yrs70-74 Yrs75-79 Yrs80-84 Yrs 85+ Yrs

Influenza-Associated Hospitalizations Among Children Aged < 5 Years By Study Barker (1982) Neuzil (2000) Izurieta (2000) Neuzil (2002) Thompson (2004) Iwane (2004) Study Hospitalizations Per 1,000 Person Years

Excess P&I Hospitalization Rates By Risk Status Barker & Mullooly (1980, 1982) Age (Years) Excess P&I Hospitalizations Per 100,000 Persons Low RiskHigh Risk

Other Influenza-Associated Morbidity Nichol et al (1999) LAIV Trial Aged –Severe febrile illness –Work days missed –Doctors visits –Antibiotic use Bridges at al (2000) TIV Trial Aged –Febrile illness –Worked days missed –Doctors visits

Summary and Recommendations Influenza infections are associated with substantial morbidity and mortality every year –Improve vaccine coverage for at-risk populations currently recommended for annual influenza vaccination by ACIP The very elderly are at substantially increased risk for influenza-associated morbidity and mortality –Encourage development of vaccines with improved immunogenicity for older adults The aging of the US population is leading to substantially more seasonal influenza-associated morbidity and mortality every year –Prepare public health officials for the increasing burden of disease associated with seasonal influenza over the next decade